Polyethylene Glycol

Absorption

PEGs can be absorbed by the gastrointestinal tract following oral administration with the fraction absorbed being dependent on the molecular weight of the compound . It is likely to display minimal absorption through the intact skin, but may penetrate through injured skin with compromised barrier function .

Absorption

PEG has low toxicity profile with an absorption of less than 0.5% .
Topical absorption of PEG occurs and, demonstrates a molecular weight dependence similar to that of PEG given orally. Absorption by this route is likely to be poor .

Absorption

Following a two-day split-dosing regimen of an oral suspension containing 140 grams of PEG 3350 in healthy subjects, the mean Cmax was 2.7 mcg/mL and the mean Tmax was 3 hours. Typically, polyethylene glycols with a high molecular weight are poorly absorbed from the gastrointestinal tract following oral administration.

Toxicity

The oral LD50 of PEG 3350 in rats is 22000 mg/kg.
There is limited clinical information on the overdose of polyethylene glycols. Based on the pharmacological action of the compound, severe diarrhea may be suspected. Overdose of polyethylene glycols should be responded with symptomatic and supportive care.

Toxicity

PEG of different molecular weights by a range of routes has been studied extensively, and has not led to any major toxicities, and signs/symptoms of toxicity that do occur are only observed at a much higher than therapeutic dose .
LD50 = 157000 mg/kg, intragastric, guinea pigs LD50 = 28915 mg/kg, intragastric, mice, rats LD50 = 9708 mg/kg, intra-abdominal, rats LD50= 7312 mg/kg, intravenous, rats

Toxicity

Oral LD50 in rat and mouse are 27500 mg/kg and 31000 mg/kg, respectively . Dermal LD50 is reported to be 20000 mg/kg in rabbit . PEGs and their derivatives are not known to cause ocular and dermal irritation, and are associated with low acute and chronic toxicities .

Description

Polyethylene glycols are a family of linear polymers formed by a base-catalyzed condensation reaction with repeating ethylene oxide units being added to ethylene. The molecular formula is (C2H4O)multH2O where mult denotes the average number of oxyethylene groups. The molecular weight can range from 200 to several million corresponding to the number of oxyethylene groups. The higher-molecular-weight materials (100 000 to 5 000 000) are also referred to as polyethylene oxides. The average molecular weight of any specific polyethylene glycol product falls within quite narrow limits (°5%). The number of ethylene oxide units or their approximate molecular weight (e.g., PEG-4 or PEG-200) commonly designates the nomenclature of specific polyethylene glycols. Polyethylene glycols with amolecular weight less than 600 are liquid, whereas those of molecular weight 1000 and above are solid. These materials are nonvolatile, water-soluble, tasteless, and odorless. They are miscible with water, alcohols, esters, ketones, aromatic solvents, and chlorinated hydrocarbons, but immiscible with alkanes, paraffins, waxes, and ethers.

The Uses of Polyethylene Glycol

Used in conjunction with carbon black to form a conductive composite.1 Polymer nanospheres of poly(ethylene glycol) were used for drug delivery.2

Indications

Indicated as a lubricant in over-the-counter ophthalmic solutions to temporarily relieve redness, burning and irritation of the eyes.

Background

Polyethylene glycols (PEGs) are products made of condensed ethylene oxide and water that can contain various derivatives and have various functions. Because many PEG types are hydrophilic, they are favorably used as enhancers of penetration, and used heavily in topical dermatological preparations. PEGs, along with their many nonionic derivatives, are widely utilized in cosmetic products as surfactants, emulsifiers, cleansing agents, humectants, and skin conditioners.
Polyethylene glycol 400 (PEG 400) is a low-molecular-weight grade of polyethylene glycol with a low-level toxicity. It is very hydrophilic, which renders it a useful ingredient in drug formulations to augment the solubility and bioavailability of weakly water-soluble drugs. It is used in ophthalmic solutions for the relief of burning, irritation and/or discomfort that follows dryness of the eye . PEG "400" indicates that the average molecular weight of the specific PEG is 400 .
PEGylation occurs when PEGs are attached to numerous protein medications, allowing for greater solubility for selected drugs. Examples of PEGylated medications are PEG-interferon alpha (Pegintron) and PEG-filgrastim. In addition, PEG is available as a bowel preparation for colonoscopy procedures and as a laxative .

Indications

PEG-400 has been indicated for the temporary relief of burning and irritation due to dryness of the eye, andfor protection against further irritation and desiccation , , .

Indications

Polyethylene glycol is indicated for use as an over-the-counter osmotic laxative to relieve occasional constipation. When used in combination with sodium ascorbate, sodium sulfate, ascorbic acid, sodium chloride and potassium chloride, it is used for cleansing of the colon in preparation for colonoscopy in adults.

What are the applications of Application

PEG 10000 is a compound used to modify therapeutic proteins and peptides to increase their solubility

Background

Polyethylene glycol (PEG) is a synthetic polymer produced via polymerization of ethylene oxide molecules to make joining units of ethylene glycol by an ether linkage. PEGs are water-soluble polymers that can form hydrogen bonds in a ratio of 100 water molecules per one PEG molecule. Molecular weights of PEGs vary by time of the polymerization process and the molecular weight represents the weighted average of the individual PEG molecules. PEGs differ in their physical and chemical properties depending on their molecular weight: PEGs are liquids when molecular weights are <1000 and the molecule turns to waxy solids with increasing molecular weights. The most common preparations of PEGs include PEG 3350 and PEG 400. PEGs have various applications in many fields, ranging from medical to industrial areas. PEGs have a long history of gastroenterology: PEG 3350 is a common over-the-counter osmotic laxative used to relieve occasional constipation. PEG 3350 is also used for cleansing of the colon in preparation for colonoscopy in adults.
The rationale of using PEG in gastroenterology is due to the physical properties of the compound: its potent water-binding capacity, negligible intestinal absorption with increasing molecular mass, lack of significant toxicity, and limited intestinal enzymatic degradation or bacterial metabolism all make PEG a useful therapeutic agent for the treatment of occasional constipation and bowel cleansing for preparation in colonoscopy.

Background

Polyethylene glycol 300 (PEG 300) is a water-miscible polyether with an average molecular weight of 300 g/mol. It is a clear viscous liquid at room temperature with non-volatile, stable properties . Polyethylene glycols are widely used in biochemistry, structural biology, and medicine in addition to pharmaceutical and chemical industries. They serve as solubilizers, excipients, lubricants, and chemical reagents. Low molecular weight glycols are observed to exhibit antibacterial properties as well. PEG 300 is found in eye drops as a lubricant to temporarily relieve redness, burning and irritation of the eyes.

What are the applications of Application

PEG 20000 is a hydrophobic polymer

What are the applications of Application

PEG 8000 Powder is a compound used to modify therapeutic proteins and peptides to increase their solubility.

What are the applications of Application

PEG 1000 is a polymer used to precipitate proteins, viruses, DNA and RNA

What are the applications of Application

PEG 35000 is a chemical polymer

What are the applications of Application

PEG 6000 is a compound used to modify therapeutic proteins and peptides to increase their solubility

Pharmacokinetics

The osmotic effect of PEG produces a copious watery diarrhea. The onset of action of PEG 3350 is about 1 to 2 hours after oral ingestion. The colonic transit of polyethylene glycol occurs in a dose-dependent manner. When used for bowel preparation before colonscopy, electrolytes are typically added in the oral solution to prevent dehydration and electrolyte disturbances. As an over-the-counter laxative, the OTC product does not contain any salts that can be absorbed. In a study involving healthy subjects, PEG 3350 had negligible effects on colonic fluid absorption or with the ability of the colonic mucosa to generate and sustain steep electrochemical gradients.

Pharmacokinetics

PEGs act as nonionic surfactant to decrease surface tension and condition the stratum corneum, thus enhance the diffusion of other molecules or drugs through the skin .

Pharmacokinetics

PEG, when used as PEG-400 for eye lubrication provides relief of dry eye symptoms and prevents further irritation, thus protecting the eye from injury . PEG allows comfortable eye drop/natural tear instillation by offering improved spreading of the drop over the ocular surface with diminished blurring .

Metabolism

Proportion of absorbed PEGs may be metabolized to lower oligomers, glycolic acid, hydroxyglycolic acids and the diglycolic acids homologs, carbon dioxide that is exhaled, and to a minor extent, oxalic acid .

Metabolism

Polyethylene glycol is a metabolically inert laxative that does not undergo intestinal enzymatic degradation or bacterial metabolism.

Metabolism

The metabolism of PEG involves the oxidation of the alcohol groups located on the PEG to a carboxylic acid. For example, the diacid and hydroxyl acid metabolites of PEG have been measured in the plasma and urine of burn patients and rabbits and in the bile of cats. In the isolated guinea pig liver and in rat/guinea pig in vitro, PEG has demonstrated to be sulfated. Evidence from experiments with PEG400 suggests that ethylene glycol is not formed as a metabolite of PEG in humans. Negligible amounts of oxalic acid are liberated after the metabolism of PEG .
The first phase of metabolism of PEG in mammals is regulated by the enzyme alcohol dehydrogenase. Liver cytochorome P450 enzymes may also play a role in the oxidation of PEG, although the evidence for this is not clear . Also, PEG has been shown to be metabolized by sulfotransferase enzymes. Although there is evidence that PEG can be metabolized to various phase 1 and phase 2 metabolites, the toxicology data presented above indicate that these metabolites are of very little toxicological concern. However, metabolism of PEG to the acid metabolite(s) has been implicated in the acidosis and hypercalcemia observed in patients after overdose . It is clear that these metabolites can be formed in multiple toxicology species and that the phase 1 metabolites are seen in animals and humans. These data indicate that humans and animals will be exposed to similar metabolites after administration of PEG . metabolic clearance of PEG decreases markedly as molecular weight increases. For PEG400, up to 25% of the dose may be metabolized in humans (Schaffer et al., 1950); similar results are also seen in the rabbit .
The absorption of PEG by the oral route is molecular weight- dependent. Urinary recovery data for PEG400 indicate that 50 to 60% of PEG with this molecular weight is absorbed from the intestine . In the case of PEG-400, up to 25% of the dose may be metabolized in humans. Similar results have also been obtained in studies on the rabbit .